# Research progress on bleeding risk assessment models in anticoagulant therapy

**Authors:** Li Sen, Xiong Kangpin, Liu Yihui

PMC · DOI: 10.3389/fcvm.2025.1645823 · Frontiers in Cardiovascular Medicine · 2025-11-11

## TL;DR

This review examines how well bleeding risk models work for patients on different anticoagulants and highlights the need for better, more adaptable tools.

## Contribution

The paper evaluates recent advancements in bleeding risk models for AF and VTE patients, emphasizing drug-specific and biomarker-integrated approaches.

## Key findings

- Traditional models like HAS-BLED and HEMORR2HAGES show moderate accuracy for NOAC-treated AF patients.
- Biomarker-integrated models like ABC and NOAC-specific DOAC score improve risk stratification.
- VTE-specific models like IMPROVE and RIETE better address dynamic risks in this population.

## Abstract

Balancing thromboembolic prevention against bleeding complications remains a critical challenge in anticoagulant therapy. While established bleeding risk assessment models (RAMs) such as HAS-BLED and HEMORR2HAGES were initially developed for warfarin-treated patients, their applicability to non-vitamin K antagonist oral anticoagulant (NOAC) users and venous thromboembolism (VTE) populations remained uncertain. This review synthesized recent advancements in bleeding risk stratification for atrial fibrillation (AF) and VTE patients, focusing on model performance, drug-specific adaptations, and emerging biomarker-driven approaches. For AF patients, traditional RAMs (HAS-BLED, HEMORR2HAGES, ATRIA) demonstrated moderate predictive accuracy (AUC: 0.55–0.74) in NOAC cohorts, with HEMORR2HAGES showing superior discrimination in certain studies. The biomarker-integrated ABC (incorporating GDF-15, troponin, hemoglobin) and the NOAC-specific DOAC score, have shown improved risk stratification, with the latter demonstrating a higher C-statistic than HAS-BLED. In VTE populations, the IMPROVE (AUC: 0.62–0.73) effectively identified high-risk medical inpatients, while the RIETE (major bleeding incidence: 0.1%–6.2%) and EINSTEIN (C-statistic: 0.68–0.74) addressed dynamic risks during anticoagulation. However, heterogeneity in validation cohorts, endpoint definitions (e.g., ISTH vs. TIMI criteria), and static risk factor selections limited cross-model generalizability. Current RAMs exhibited variable performance across anticoagulant regimens and clinical contexts highlighting the need for next-generation models that integrate dynamic risk modifiers (e.g., transient anemia, antiplatelet use) and biomarker-based approaches. While NOAC-specific tools such as the DOAC may be more appropriate for AF patients, context-adapted models like IMPROVE and RIETE are better suited for VTE populations. Future research should prioritize real-world validation, machine learning integration, and the standardization of bleeding definitions to advance precision anticoagulation strategies.

## Linked entities

- **Proteins:** GDF15 (growth differentiation factor 15), LOC115584584 (troponin C, skeletal muscle)
- **Diseases:** atrial fibrillation (MONDO:0004981), venous thromboembolism (MONDO:0005399)

## Full-text entities

- **Genes:** GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}
- **Diseases:** anemia (MESH:D000740), AF (MESH:D001281), VTE (MESH:D054556), thromboembolic (MESH:D013923), bleeding (MESH:D006470)
- **Chemicals:** NOAC (-), warfarin (MESH:D014859)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12644015/full.md

## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12644015/full.md

---
Source: https://tomesphere.com/paper/PMC12644015